Guyton Chapter 31; Acid Base Regulation
There are 3 main ways of regulating H+ conc. in the body:
1) Acid-Base buffer systems / chemical buffers
2) Respiratory center
3) Kidneys
The acid-base buffers/chemical buffers are divided into 3 main types:
1) Bicarbonate buffer-
a. This depends on H2CO3 and NaHCO3.
b. CO2 + H2O give H2CO3, which then dissociates into H+ and HCO3- ions.
c. This process requires carbonic anhydrase.
d. NaHCO3 in solution dissociates into Na+ and HCO3-.
e. H2O + CO2 > H2CO3 > H+ + HCO3-
f. ↑Acid/H+ in the body > Above equation moves in the opposite direction > H+ ions bind
with HCO3- ions and form H2CO3 > The carbonic acid breaks down into H2O and CO2 > ↑
CO2 is detected by the respiratory center > ↑Respiratory rate and the CO2 is lost > Overall
pH is returned to normal.
g. NaOH + H2CO3 > NaHCO3 + H2O > Na+ + HCO3- + H+
h. ↑Base/OH- in the body > Above reaction takes place > Carbonic acid mops up the OH-
ions > Carbonic acid required for this reaction comes from CO2 > Therefore, ↓CO2 >
Respiratory center gets depressed > ↓Rate of respiration > In addition, ↑HCO3- > pH
returns to normal.
¿
i. Henderson Hasselbach equation- pH=6.1+ HCO 3− 0.03 x PCO 2 ¿ where 6.1 is the pK.
j. When the pH=pK (both are 6.1), the buffer has equal concentrations of both HCO3- and CO2
(the amount of CO2 reflects the amount of carbonic acid). In other words, a buffer should
work at its best when the pH equals the pK.
k. However, in the body, the normal pH is 7.4, which means that with this buffer system, at
this pH the HCO3- is about 20 times more in quantity than the H+ ions.
l. Despite this gross imbalance, the bicarbonate buffer system is the most powerful buffer
system in the body, because the concentrations of these 2 substances is very tightly
regulated by the body.
2) Phosphate Buffer System:
a. This system depends on H2PO4-, a weak acid, and HPO4-2, a weak base.
b. Na2HPO4 + HCl > NaH2PO4 + NaCl
c. When ↑Acid > H+ binds with HPO4-2 and converted to H2PO4- >↓Strong acid (HCl),
↑Weak acid (H2PO4-) > pH is returned to normal.
d. NaH2PO4 + NaOH > Na2HPO4 + H2O
e. When ↑Base > OH- binds with H2PO4- and is converted to HPO4-2 > ↓Strong base
(NaOH), ↑Weak base (HPO4-2).
f. This buffer system is particularly stronger in the kidney tubules as well as the ICF. This is
because in both of these there is a higher conc. of phosphate, and a lower pH (bringing it
close to the pK, 6.8, where this system works best).
3) Protein Buffer System:
a. This is mainly an intracellular buffer system.
, b. It works well in the cells due to its high concentration and again, the pK of this system is
close to the relatively lower pH inside the cells.
c. Takes longer to be effective as H+ and HCO3- diffuse across membranes very slowly (except
for in RBCs).
All the buffer systems affect each other, by exchanging H+ ions amongst themselves. This is known as the
isohydric principle.
Respiratory Buffer System:
This and the renal buffer systems are physiological buffers.
Controlled by alveolar ventilation. ↑CO2 formation, so ↓pH, so ↑alveolar ventilation until pH almost
returns to normal. The opposite happens when pCO2 is reduced (normal pCO2= 40mmHg).
When ↑pH due to ↑pCO2 and ↓ventilation, the ↓O2 levels as well, and so ventilation can’t go down too
much, making the system less effective at dealing with increased pH than with decreased.
Abnormal respiration can lead to abnormal pH, conditions called respiratory acidosis and alkalosis.
Renal Buffer System:
About 80 mEq of wasteful non-volatile acids are produced by the body every day. This is removed by the
renal tubules as H+ ions through secretion.
About 4320 mEq of HCO3- ions are filtered into the renal tubules every day. Normally, almost all of this has
to be reabsorbed.
In order to reabsorb a HCO3- ions, it has to be combined with a H+ ion, ie, to reabsorb the 4320 mEq of
HCO3- ions, 4320 mEq of H+ ions are required to be secreted.
Total H+ secreted per day = 4320 (to bind with HCO3- and reabsorb it) + 80 (waste non-volatile acids) =
4400 mEq.
Therefore, the amount of H+ ions secreted and HCO3- ions reabsorbed are almost equal. We say that the
H+ (acid) and HCO3- (base) titrate each other.
Acidosis occurs > H+ in excess compared to HCO3- > Titration of H+ and HCO3- to reabsorb HCO3- occurs
> Excess leftover secreted H+ is excreted from the body > pH returns to normal.
Alkalosis occurs > HCO3- ions in excess compared to H+ > Titration of H+ and HCO3- to reabsorb HCO3-
occurs > Excess leftover filtered HCO3- is excreted from the body > pH returns to normal.
Therefore, when the ion in deficit is unable to neutralize the one in excess, i.e. Incomplete titration occurs,
the ion in excess is excreted.
There are 3 main intertwined mechanisms through which renal buffering is regulated:
1. H+ Secretion:
CO2 diffuses into renal tubules > CO2 + H2O (+carbonic anhydrase) → H2CO3 > H2CO3 → H+ + HCO3- >
H+ is secreted into lumen > HCO3- is absorbed into blood.
H+ is secreted via a Na+/H+ counter-transporter in the proximal tubules, and via H+ ATPase and H+/K+
ATPase transporter in the distal (type A intercalated cells) and collecting tubules.
There are 3 main ways of regulating H+ conc. in the body:
1) Acid-Base buffer systems / chemical buffers
2) Respiratory center
3) Kidneys
The acid-base buffers/chemical buffers are divided into 3 main types:
1) Bicarbonate buffer-
a. This depends on H2CO3 and NaHCO3.
b. CO2 + H2O give H2CO3, which then dissociates into H+ and HCO3- ions.
c. This process requires carbonic anhydrase.
d. NaHCO3 in solution dissociates into Na+ and HCO3-.
e. H2O + CO2 > H2CO3 > H+ + HCO3-
f. ↑Acid/H+ in the body > Above equation moves in the opposite direction > H+ ions bind
with HCO3- ions and form H2CO3 > The carbonic acid breaks down into H2O and CO2 > ↑
CO2 is detected by the respiratory center > ↑Respiratory rate and the CO2 is lost > Overall
pH is returned to normal.
g. NaOH + H2CO3 > NaHCO3 + H2O > Na+ + HCO3- + H+
h. ↑Base/OH- in the body > Above reaction takes place > Carbonic acid mops up the OH-
ions > Carbonic acid required for this reaction comes from CO2 > Therefore, ↓CO2 >
Respiratory center gets depressed > ↓Rate of respiration > In addition, ↑HCO3- > pH
returns to normal.
¿
i. Henderson Hasselbach equation- pH=6.1+ HCO 3− 0.03 x PCO 2 ¿ where 6.1 is the pK.
j. When the pH=pK (both are 6.1), the buffer has equal concentrations of both HCO3- and CO2
(the amount of CO2 reflects the amount of carbonic acid). In other words, a buffer should
work at its best when the pH equals the pK.
k. However, in the body, the normal pH is 7.4, which means that with this buffer system, at
this pH the HCO3- is about 20 times more in quantity than the H+ ions.
l. Despite this gross imbalance, the bicarbonate buffer system is the most powerful buffer
system in the body, because the concentrations of these 2 substances is very tightly
regulated by the body.
2) Phosphate Buffer System:
a. This system depends on H2PO4-, a weak acid, and HPO4-2, a weak base.
b. Na2HPO4 + HCl > NaH2PO4 + NaCl
c. When ↑Acid > H+ binds with HPO4-2 and converted to H2PO4- >↓Strong acid (HCl),
↑Weak acid (H2PO4-) > pH is returned to normal.
d. NaH2PO4 + NaOH > Na2HPO4 + H2O
e. When ↑Base > OH- binds with H2PO4- and is converted to HPO4-2 > ↓Strong base
(NaOH), ↑Weak base (HPO4-2).
f. This buffer system is particularly stronger in the kidney tubules as well as the ICF. This is
because in both of these there is a higher conc. of phosphate, and a lower pH (bringing it
close to the pK, 6.8, where this system works best).
3) Protein Buffer System:
a. This is mainly an intracellular buffer system.
, b. It works well in the cells due to its high concentration and again, the pK of this system is
close to the relatively lower pH inside the cells.
c. Takes longer to be effective as H+ and HCO3- diffuse across membranes very slowly (except
for in RBCs).
All the buffer systems affect each other, by exchanging H+ ions amongst themselves. This is known as the
isohydric principle.
Respiratory Buffer System:
This and the renal buffer systems are physiological buffers.
Controlled by alveolar ventilation. ↑CO2 formation, so ↓pH, so ↑alveolar ventilation until pH almost
returns to normal. The opposite happens when pCO2 is reduced (normal pCO2= 40mmHg).
When ↑pH due to ↑pCO2 and ↓ventilation, the ↓O2 levels as well, and so ventilation can’t go down too
much, making the system less effective at dealing with increased pH than with decreased.
Abnormal respiration can lead to abnormal pH, conditions called respiratory acidosis and alkalosis.
Renal Buffer System:
About 80 mEq of wasteful non-volatile acids are produced by the body every day. This is removed by the
renal tubules as H+ ions through secretion.
About 4320 mEq of HCO3- ions are filtered into the renal tubules every day. Normally, almost all of this has
to be reabsorbed.
In order to reabsorb a HCO3- ions, it has to be combined with a H+ ion, ie, to reabsorb the 4320 mEq of
HCO3- ions, 4320 mEq of H+ ions are required to be secreted.
Total H+ secreted per day = 4320 (to bind with HCO3- and reabsorb it) + 80 (waste non-volatile acids) =
4400 mEq.
Therefore, the amount of H+ ions secreted and HCO3- ions reabsorbed are almost equal. We say that the
H+ (acid) and HCO3- (base) titrate each other.
Acidosis occurs > H+ in excess compared to HCO3- > Titration of H+ and HCO3- to reabsorb HCO3- occurs
> Excess leftover secreted H+ is excreted from the body > pH returns to normal.
Alkalosis occurs > HCO3- ions in excess compared to H+ > Titration of H+ and HCO3- to reabsorb HCO3-
occurs > Excess leftover filtered HCO3- is excreted from the body > pH returns to normal.
Therefore, when the ion in deficit is unable to neutralize the one in excess, i.e. Incomplete titration occurs,
the ion in excess is excreted.
There are 3 main intertwined mechanisms through which renal buffering is regulated:
1. H+ Secretion:
CO2 diffuses into renal tubules > CO2 + H2O (+carbonic anhydrase) → H2CO3 > H2CO3 → H+ + HCO3- >
H+ is secreted into lumen > HCO3- is absorbed into blood.
H+ is secreted via a Na+/H+ counter-transporter in the proximal tubules, and via H+ ATPase and H+/K+
ATPase transporter in the distal (type A intercalated cells) and collecting tubules.
